DED has a high incidence worldwide and is the main reason why ophthalmic patients seek treatment.
24 In addition to dryness, foreign body sensation, and visual fatigue,
4 patients with severe disease may suffer from visual impairment.
25 Moreover, long-term eye discomfort may also affect the patients’ physical and mental health,
26,27 which has attracted considerable attention from the academic community. The onset of DED may involve desiccation and osmotic stress caused by one or more factors.
28 Inflammation caused by ocular surface injury and hyperosmolarity affects corneal epithelial cells and immune cells.
29 Disruption of inflammatory factor secretion further leads to reduced mucus secretion and unstable tear film, aggravating the occurrence of dry eye.
30 Pyroptosis, a type of programmed cell death that can affect the inflammatory cycle, is considered a key process induced by GSDMD. This process is regulated by caspase-1 and plays an important role in the pathogenesis of dry eye.
31 A variety of inflammation- and pyroptosis-related factors, including ASC, procaspase-1, IL-1β, and IL-18,
32 regulate the downstream immune response,
33 activate caspase-1 to lyse GSDMD and ultimately lead to pyroptosis.
34,35 Chen et al. reported that NLRP4 and NLRP12 cooperate synergistically to promote pyroptosis and aggravate DED in a GSDMD-dependent manner.
9 GSDME was originally identified in 2017.
12 Later, Rogers et al. confirmed that the cleavage of GSDME by caspase-3 leads to cell death and cell membrane rupture.
13 Researchers have subsequently focused on the role of pyroptosis caused by the cleavage of GSDME by caspase-3 in treating tumors and immune diseases.
15,16,36 Notably, the extent of GSDME-mediated pyroptosis is much greater than that of GSDMD in cholestatic hepatitis.
20 Therefore, the role of GSDME-mediated pyroptosis in DED is worthy of further exploration.